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Question 1

What is calcium responsible for or regulate?

Answer 1

FertilisationProliferationSecretionNeurotransmissionMetabolismLearning and memoryApoptosis and necrosis

Question 2

Why do calcium levels have to be closely controlled?

Answer 2

Ca cannot be metabolised therefore have to move it in and out of the cytoplasm

Question 3

What are the advantages and disadvantages to a steep Ca concentration gradient?

Answer 3

Advantages – Increases in Ca concentration occurs rapidly with little Ca movementDisadvantages – Ca overload leads to loss of regulation and cell death

Question 4

What does the set up and maintenance of a Ca gradient rely on?

Answer 4

1. Impermeable membrane2. Ability to expel Ca across membrane using: — Ca ATPase and Na-Ca exchanger3. Ca buffers4. Intracellular Ca stores — rapidly and non rapidly releasable

Question 5

How is the permeability of the membrane regulated?

Answer 5

Is regulated by the open or close state of ion channels

Question 6

Describe the action of the Ca ATPase

Answer 6

Moves Ca out at the expense of ATP so against a chemical. And concentration gradient

Question 7

Describe the feedback mechanism for Ca ATPase What characteristic for affinity and capacity does it have?

Answer 7

An increase in [Ca] occurs and Ca binds to calmodulin (trigger protein) The Ca-calmodulin complex binds to Ca-ATPase The Ca-ATPase removes Ca from the cell – high affinity and low capacity

Question 8

Describe the action of the Na/Ca exchanger. What capacity and affinity does the channel have?

Answer 8

[Na] is into the cell, so it is used as the driving force using a Na-K-ATPase Antiporter is electrogenic so it removes calcium best at a resting potential Allows for Ca to be removed against its concentration gradientLow affinity with a high capacity (Good at high concentrations)

Question 9

What do calcium buffers do?

Answer 9

Limits calcium diffusion in the cell– independently regulates the movement of ions

Question 10

What are the effects of calcium buffers?Name some Ca buffersWhat happens when there is an incresed saturation for the buffers?How far can a Ca ion normally diffuse before it encounters a buffer molecule?

Answer 10

Ca diffuses more slowly. Calreticulin, calbindin and calsequestrin Ca can diffuse further in the cell because it is not limited by the bufferNormal amount of diffusion to reach a binding molecule is 0.1 -0.5 micrometres

Question 11

How is the [Ca] elevated then returned to normal levels?

Answer 11

1. Ca influx across the membrane through specific channels— voltage gated channels and receptor-operated ion channels2. Ca is released from rapidly releasable stores — G-protein coupled receptors and calcium induce Ca release3. Non-rapidly releasable stores

Question 12

Describe the two ways that Ca influx occurs across a plasma membrane

Answer 12

Voltage operated Ca channels– senses depolarisation which opens an aqueous pore to allow Ca into the cellIonotropic receptors (receptor-operated ion channels)– e.g. NMDA receptors for glutamate and nicotinic ACh receptors

Question 13

What facilitates the relates of Ca from rapidly releasable stores?How does in it get Ca into the store?What is the concentration of Ca inside the stores?

Answer 13

SERCA pump – sarcoplasmic/endoplasmic reticulum Ca2+ ATPase Uses ATP to bring Ca in against its steep gradient. The Ca binds to calsequestrin. The release of Ca is controlled by release channels. Concentration = 1mM

Question 14

What are the two ways that the release of Ca from intracellular stores is controlled?

Answer 14

1. G-protein coupled receptors 2. Calcium induced calcium release

Question 15

Describe the process of calcium release via G-protein receptorsWhere are G-protein receptors found?What proportion of drugs target these receptors?

Answer 15

Molecule binds to receptor which interacts with a G-protein which mediate the release of effector molecules inside the cell. Majority of cells contain G-protein receptors30-50% of drugs target these receptors

Question 16

What molecules can stimulate GPCR mediated signalling?How are G-proteins activated?

Answer 16

Hormones, neurotransmitters, ions, odourants, taste Are heterotrimeric proteins which splits into subunits when it is activated

Question 17

What subunits does a heterotrimeric g-protein split into?

Answer 17

Alpha subunit either affects phospholipase C or adenylyl cyclase– Alpha(q) affects phospholipase C which produces IP3 and diacylglycerol– Alpha(s) and (i) are effectors of adenylyl cyclase, which generates cAMP (secondary messenger) which activates protein kinase A Beta subunit with gamma subunit affects ions channels

Question 18

What does g-protein alpha(q) do?

Answer 18

Breaks down PIP2, a component of membrane phospholipid – this releases IP3 which stimulates IP3 receptors on SR/ER – induces release of intracellular stores of Ca E.g. Muscarinic M3 receptor in smooth muscle of airways –> contraction of bronchioles

Question 19

How does calcium induced calcium release occur?Give a characteristic of ryanodine receptors.

Answer 19

Calcium influx into a cell will bind to ryanodine receptors on the surface of SR/ER.This causes Ca to be released from the SR/ER Ryanodine receptors are not endogenous to humans – are a plant alkaloid

Question 20

Where are ryanodine receptors commonly found?Where are they located in the cell?What does the release of Ca around the contractile proteins allow for?

Answer 20

Cardiac myocytesNear to membranes A strong coordinated contractile event

Question 21

Describe the process of depolarisation in cardiac myocytes

Answer 21

Depolarisation occurs along the cardiac myocytes which causes Na channels to open, allowing Na to move from t-tubules into the cell. The Na influx causes Voltage gated Ca channels to open. The influx of Ca binds to ryanodine receptors, causing Ca to be released from the ER. Increased [Ca] causes heart contraction.

Question 22

What percentage of the contraction process is stimulated by the influx and the intracellular store?

Answer 22

85% from intracellular stores15% from calcium influx

Question 23

How is calcium removed from the cell after depolarisation?

Answer 23

MINOR ROUTE FOR REMOVALThe Na/Ca exchanger will favour the outflow of calcium when repolarisation starts, in order to lower the high [Ca] from the cell. MAJOR ROUTE FOR REMOVALThe SERCA pump will pump calcium back into the ER/SR to prepared for another release event.

Question 24

What allows for the prolongation of polarisation in cardiac cells?

Answer 24

1. Ca channels show slower activation and inactivation the Na channels2. Low K conductance at depolarised potentials

Question 25

How does calcium control skeletal muscle contraction?

Answer 25

Calcium binds to troponin which undergoes a conformational change, which moves tropomyosin to reveal the actin binding sites for myosin head groups.

Question 26

What occurs in skeletal muscle in the presence of ATP?

Answer 26

Myosin undergoes cycles of attachment and detachment alongside the movement of myosin head groups, causes the sliding of actin along myosin bundles to contract the myocyte.

Question 27

Where are non-rapidly releasable stores of calcium held?What type of signalling do they take part in and why?

Answer 27

In the mitochondria Normal Ca signalling due to micro domains – they sense high levels of Ca as they are close to Ca channels.

Question 28

How do the mitochondria take up calcium?Give some characteristics of the channels.

Answer 28

Using energy from the respiratory chain proton production – are uniporters– low affinity but high capacity

Question 29

What are the roles of mitochondrial calcium uptake?

Answer 29

1. Regulate calcium buffering2. Regulate the pattern and extent of Ca signalling3. Stimulate mitochondrial metabolism – matches demand and energy supply4. Has a role in apoptosic cell death – due to altered redox potential

Question 30

Wy must calcium levels be restored to a cell quickly?How does it do this?

Answer 30

Allows muscle cells to relax Stops the release of excess neurotransmitter Cells use transient signals – levels only increase for a sort period of time

Question 31

How does the [Ca] return to normal?

Answer 31

Signal is terminatedCalcium is removedCalcium stores are refilled

Question 32

How are calcium stores refilled?

Answer 32

1. Recycling of released cytosolic Ca (in cardiac myocytes)2. Capacitative Ca entry – ER sends out a depleted signal in order to refill the Ca stores which are preferentially used

Question 33

What emits the “depleted signal” from the SR/ER? What can this entry regulate?

Answer 33

STIM – located in ER membrane, is a Ca sensor– tail sits in store and binds to Ca– when [Ca] is low, conformational change occurs– low [Ca] stimulates the opening of ORAIORAI – plasma membrane channel to allow Ca entry Regulates physiological processes